Obesity is a risk factor for numerous adult diseases including hypertension, diabetes, hyperlipidemia and ischemic heart disease. Since most of these are chronic conditions, they are expected to lead to rising medical costs and to create serious problems for society.
Anti-obesity drugs are being developed for prevention, and currently several appetite suppressors and lipid absorption inhibitors are being used in the clinic. Some of the known target molecules in anti-obesity research include leptin, PPARγ and neuropeptide Y, but because of the huge variety of causes for obesity, it is desirable to focus on molecules having different action mechanisms as targets for future drug development.
Proper diagnosis of obesity and its causes is essential for appropriate treatment thereof, and therefore identification of a convenient and high-precision obesity marker has been desired. With the discovery in recent years that the effects of administered drugs are partially dependent on patient genotypes including genetic polymorphism, it has become a goal to establish examination methods and diagnostic markers on the molecular level for clinical trials at the drug development stage, for so-called “tailor-made medicine”.
Biosynthesis of fatty acids is mediated by acetyl CoA carboxylase and fatty acid synthases. LCE (Accession No. NM—024090 (human; SEQ ID NO: 1); NM—130450 (mouse; SEQ ID NO: 2)) is one such fatty acid synthase, and in the fatty acid synthesis pathway in which synthesis is initiated on the substrate acetyl CoA, LCE is known to catalyze elongation of the carbon chains primarily of C12 and longer fatty acids, including myristic acid from lauric acid, palmitic acid from myristic acid, stearic acid from palmitic acid and vaccinic acid from palmitoleic acid (J. Biol. Chem., 276(48), 45358-45366(2002); Non-patent document 1).
For example, WO02/44320 (Patent document 1) teaches that ELG5 (LCE) exhibits activity as an elongase on polyunsaturated fatty acid (PUFA) substrates. It also describes a connection between elongases and diseases such as diabetes, citing a report showing that elongase activity is accelerated in the livers of STZ-induced diabetic rat models (Suneja et al., 1990, Biochem. Biophys. Acta, 1042:81-85; Non-patent document 2).
It has also been reported that feeding of mice alters expression levels of mouse FACE (LCE) (Matsuzaka T. et al., J. Lipid Res., 43(6): 911-20 (2002); Non-patent document 3).
Patent document 1: WO02/44320
Non-patent document 1: J. Biol. Chem., 276(48), 45358-45366(2002)
Non-patent document 2: Suneja et al., 1990, Biochem. Biophys. Acta, 1042:81-85
Non-patent document 3: Matsuzaka T. et al., J. Lipid Res., 43(6): 911-20 (2002)